Biochem 1

• What is the pH range for normal plasma pH?

  7.36-7.44
• Why is a weak acid 50% dissociated at a pH equal to its pKa?

  Because half is in acid form, half is in base form
• What is the pKa of H2CO3 at 37°C?

  6.1
• What happens to the ratio of [A-] to HA when the pH changes from pKa to 1 pH unit below pKa?

  Changes from 1:1 to 1:10
• What is the normal range for PCO2 in the blood?

  35-45 mmHg
• Why is the bicarbonate buffer system the most important buffer in plasma?

  Because it is the primary ECF buffer
• What is the intracellular pH?

  7.1
• How does hemoglobin act as a buffer in the tissues?

  It accepts H+ formed by CO2
• What percentage of CO2 diffuses into erythrocytes from tissues?

  95%
• What is the role of carbonic anhydrase in erythrocytes?

  It forms H2CO3 from CO2 and H2O
• What is the chloride shift?

  HCO3- moves to plasma, Cl- moves to erythrocytes
• How does the respiratory center respond to acidosis?

  Increases rate and depth of respiration
• What is the isoelectric point (pI) of an amino acid?

  pH at which there is no net charge
• What is the significance of the pKa in the Henderson-Hasselbalch equation?

  It indicates the pH at which 50% dissociation occurs
• What are the essential amino acids?

  Arg, His, Ile, Leu, Thr, Lys, Met, Phe, Trp, Val
• Why is insulin considered an anabolic hormone in the context of amino acid uptake?

  It favors the uptake of amino acids by tissues
• What is the primary defect in cystinuria?

  Defective transporter for Cysteine, Ornithine, Lysine, and Arginine
• What is the clinical significance of cystine stones in cystinuria?

  They can cause kidney stones and block the urinary tract
• What is the genetic basis of Marfan syndrome?

  Mutations in the FBN1 gene on chromosome 15
• Why does Marfan syndrome lead to aortic aneurysms?

  Due to defective connective tissue in the aorta
• What is the secondary structure of a protein characterized by beta pleated sheets?

  Two or more peptide chains parallel or anti-parallel to each other
• How does the secondary structure of prion proteins differ in prion diseases?

  Higher proportion of β-sheet structure replaces α-helix
• What is the primary pathological feature of Alzheimer's disease?

  Formation of beta-amyloid plaques and neurofibrillary tangles
• Why is tau protein significant in Alzheimer's disease?

  It forms neurofibrillary tangles within neurons
• What are the major buffer systems in the body?

  • Bicarbonate-carbonic acid buffer (ECF buffer)
  • Proteins (ICF and plasma RBC)
  • Hemoglobin (red blood cells)
  • Phosphate buffer (ICF and urine buffer)
  • Ammonia (urine)
• What are the steps involved in CO2 transport and buffering in the body?

  1. CO2 diffuses into erythrocytes
  2. Carbonic anhydrase forms H2CO3 from CO2 and H2O
  3. H2CO3 dissociates into H+ and HCO3-
  4. H+ binds to hemoglobin
  5. HCO3- moves to plasma, Cl- moves to erythrocytes (chloride shift)
  6. In lungs, H+ binds with HCO3- to form H2CO3, which dissociates into CO2 and H2O
  7. CO2 is exhaled
• What are the clinical manifestations of Marfan syndrome?

  • Excessively long extremities and fingers (Arachnodactyly)
  • Pectus carinatum or pectus excavatum
  • Hypermobile joints
  • Dissecting aortic aneurysms and valvular disease
  • Dislocation of the lens (typically upward and outward and temporally)
• What are the key features of Alzheimer's disease?

  • Formation of beta-amyloid plaques (extracellular)
  • Accumulation of tau protein forming neurofibrillary tangles (intracellular)
  • Onset usually in the sixth to ninth decade of life
  • Responsible for 100,000 deaths/year in the United States
• What are the key features of prion diseases?

  • Mutated prion proteins (PrPsc, PrPr)
  • Higher proportion of β-sheet structure replaces α-helix
  • Aggregations of amyloid fibers
  • Examples: Creutzfeldt-Jakob Disease, Kuru, Amyloidosis
• What are the key features of cystinuria?

  • Defective transporter for Cysteine, Ornithine, Lysine, and Arginine (COLA)
  • Kidney stones due to cystine crystals
  • Frequency: 1 in 7000
  • Clinically can cause kidney damage and block urinary tract
• What are the key features of Hartnup disease?

  • Autosomal recessive disease affecting SLC6A19 gene
  • Defective absorption of neutral amino acids, including tryptophan
  • Clinical features: photosensitivity, intermittent ataxia, dermatitis, dementia, diarrhea
  • Attacks diminish with age
• What are the key features of protein folding and structure?

  • Primary structure: AA sequence of the polypeptide chain
  • Secondary structure: Alpha helix, beta pleated sheet, beta bend
  • Tertiary structure: 3D folding of the polypeptide chain
  • Quaternary structure: Assembly of multiple polypeptide chains
• What are the key features of amyloidosis?

  • Formation, accumulation, and deposition of insoluble fibrillar aggregates (amyloid fibrils)
  • Consisting of β-pleated sheet structures
  • Examples: Alzheimer's disease, systemic amyloidosis
• What are the key features of the bicarbonate buffer system?

  • Most important buffer in plasma (ECF buffer)
  • Involves H2CO3 and HCO3-
  • pKa of H2CO3 is 6.1 at 37°C
  • Regulated by the respiratory system (PCO2) and kidneys (HCO3-)
• What are the key features of the phosphate buffer system?

  • Important in ICF and urine
  • Involves H2PO4- and HPO42-
  • pKa of H2PO4- is 6.8
  • Effective buffer in the pH range of 6.8 ±1
• What are the key features of the protein buffer system?

  • Important in ICF and plasma (RBC)
  • Due to histidine residues
  • Effective buffer in the pH range of 7.0 ±1
  • Includes hemoglobin as a major buffering agent
• What are the key features of the hemoglobin buffer system?

  • Accepts H+ formed by CO2 in tissues
  • Releases H+ in lungs to form H2CO3
  • Most important buffer groups are histidines
  • Each globin chain contains 9 histidine residues
• What are the key features of the respiratory regulation of pH?

  • Acidosis: Increased rate and depth of respiration (hyperventilation)
  • Alkalosis: Decreased rate of respiration (hypoventilation)
  • Regulates PCO2 component of the bicarbonate buffer
  • Chemoreceptors in medulla, carotid, and aortic bodies respond to H+ and PCO2 changes
• What are the key features of the Henderson-Hasselbalch equation?

  • pH = pKa + log [A-]/[HA]
  • Describes the relationship between pH, pKa, and the ratio of conjugate base to acid
  • When pH = pKa, 50% dissociation of weak acid
  • Buffers have maximum capacity when pH = pKa
• What are the key features of amino acid titration curves?

  • Cation (+ve) at low pH
  • Anion (-ve) at high pH
  • Zwitterion (net neutral) at isoelectric point (pI)
  • pI = (pKa2 - pKa1)/2
  • Net charge depends on pH relative to pI